Equivalents of 2-Cyanoethyl Tetraisopropylphosphorodiamidite
122.5 (CH), 121.9 (CH), 115.3 (CN), 72.2 (d, J = 4.7 Hz, OCH),
11.9 Hz, O-C), 145.0 (d, J = 8.2 Hz, O-C), 140.3 (C), 140.1 (C),
61.7 (CH2), 39.1 (d, J = 6.4 Hz, CH2), 24.5 (CH2), 14.3 (CH3) ppm. 140.0 (C), 139.9 (C), 134.5 (C), 134.3 (C), 129.2 (CH), 129.1 (CH),
IR: ν
= 3054, 3028, 2986, 1737, 1489, 1362, 1301, 1290, 1025, 128.0 (CH), 127.9 (CH), 127.9 (CH), 127.6 (CH), 127.5 (CH), 127.5
˜
max
762, 700 cm–1. HRMS (ESI): m/z calcd. for C39H31NO6P [M +
H]+ 640.1889; found 640.1880. [α]2D0 = +51 (c = 1, CHCl3).
(CH), 127.2 (CH), 127.0 (CH), 126.8 (CH) 126.7 (CH), 126.1 (d, J
= 1.8 Hz, C), 125.5 (d, J = 2.6 Hz, C), 122.8 (CH), 122.7 (C), 122.5
(C), 122.3 (CH), 74.2 (d, J = 5.4 Hz, OCH), 62.7 (OCH2), 61.4
(OCH2), 37.9 (d, J = 7.4 Hz, CH2), 14.3 (CH3), 14.2 (CH3) ppm.
14aЈ: 31P NMR (202.5 Hz, CDCl3): δ = 1.7 ppm. 1H NMR
(500.1 MHz, CDCl3): δ = 8.45 (d, J = 8.5 Hz, 1 H), 8.38 (d, J =
8.5 Hz, 1 H), 7.85 (m, 2 H), 7.85 (m, 2 H), 7.71 (t, J = 7.6 Hz, 2
H), 7.65–7.61 (m, 2 H), 7.53 (s, 1 H), 7.52 (s, 1 H), 7.13–7.09 (m,
2 H), 6.95–6.92 (m, 4 H), 6.47–6.46 (m, 4 H), 5.52–5.45 (m, 1 H,
OCH), 4.12 (q, J = 7.5 Hz, 2 H, OCH2), 3.13 (dd, J = 17.0, 5.4 Hz,
1 H), 3.02–2.97 (m, 2 H), 2.86 (dd, J = 17.0, 7.0 Hz, 1 H), 1.19 (t,
J = 7.5 Hz, 3 H) ppm. 13C NMR (125.8 MHz, CDCl3): δ = 168.7
(CO), 145.9 (d, J = 12.0 Hz, O-C), 144.7 (d, J = 9.2 Hz, O-C),
140.2 (C), 140.1 (C), 139.9 (C), 139.8 (C), 134.5 (C), 134.3 (C),
IR: ν
= 2986, 2930, 1740, 1489, 1364, 1306, 1291, 1262, 1182,
˜
max
1110, 1049, 1030, 762, 751, 700 cm–1. HRMS (ESI): m/z calcd. for
C40H34O8P [M + H]+ 673.1991; found 673.2001. [α]2D0 = +95 (c =
1, CHCl3).
Phosphates 16a,aЈ: Phosphates 16 have been prepared from rac-
VANOL (0.2 mmol) and N-(tert-Butoxycarbonyl)-l-threonine
methyl
ester
N,N,NЈ,NЈ-tetraisopropylphosphorodiamidite
[(2S,3R)-10], as described for 14a,aЈ. The corresponding phosphites
129.1 (CH), 129.1 (CH), 128.1 (CH), 128.0 (CH), 127.9 (CH), 127.7 (31P NMR: δ = 154.3 and 142.3 ppm ppm) were obtained after 16 h
(CH), 127.6 (CH), 127.5 (CH), 127.4 (CH), 126.8 (C), 126.8 (C), heating at 40 °C. After oxidation, the crude mixture was purified
125.8 (d, J = 1.8 Hz, C), 125.3 (d, J = 2.8 Hz, C), 122.7 (C), 122.5
(CH), 122.3 (C), 122.1 (CH), 115.3 (CN), 72.2 (d, J = 4.7 Hz, yield). Phosphates 16a and 16aЈ were separated by semi-preparative
OCH), 61.5 (CH2), 39.0 (d, J = 4.5 Hz, CH2), 24.7 (d, J = 5.5 Hz, HPLC on Sunfire C18 column, H2O/MeCN/formic acid
= 3055, 3026, 2985, 2929, 1735, (20:80:0.1). 16a: retention time 12.0 min; 16aЈ: retention time
by chromatography on silica gel (heptane/EtOAc = 6:4 to 4:6, 78%
a
CH ), 14.2 (CH ) ppm. IR: ν
˜
max
2
3
1489, 1363, 1301, 1290, 1024, 967, 946, 762, 700 cm–1. HRMS
(ESI): m/z calcd. for C39H31NO6P [M + H]+ 640.1889; found
640.1882. [α]2D0 = –89 (c = 1, CHCl3).
15.0 min.
16a: 31P NMR (202.5 Hz, CDCl3): δ = 1.6 ppm. 1H NMR
(500.1 MHz, CDCl3): δ = 8.44 (d, J = 8.1 Hz, 1 H), 8.32 (d, J =
7.8 Hz, 1 H), 7.88 (d, J = 8.0 Hz, 1 H), 7.83 (d, J = 8.0 Hz, 1 H),
7.71–7.59 (m, 4 H), 7.53 (s, 1 H), 7.51 (s, 1 H), 7.13–7.08 (m, 2 H),
6.95–6.91 (m, 4 H), 6.47 (d, J = 7.6 Hz, 4 H), 5.54–5.49 (m, 1 H,
OCH), 4.93 (d, J = 9.6 Hz, 1 H), 4.44 (d, J = 9.6 Hz, 1 H), 3.56 (s,
3 H, OMe), 1.65 (d, J = 6.3 Hz, 3 H), 1.42 (s, 9 H, CMe3) ppm.
13C NMR (125.8 MHz, CDCl3): δ = 169.9 (CO), 155.9 (CO), 146.0
(d, J = 11.1 Hz, O-C), 145.0 (d, J = 8.3 Hz, O-C), 140.3 (C), 140.1
(C), 139.9 (C), 139.8 (C), 134.5 (C), 134.4 (C), 129.1 (CH), 128.1
(CH), 127.9 (CH), 127.8 (CH), 127.5 (CH), 127.4 (CH), 127.2
(CH), 127.0 (CH), 126.8 (CH), 126.7 (CH), 125.9 (C), 125.4 (C),
122.7 (C), 122.6 (CH), 122.5 (C), 122.2 (C), 80.4 (CMe3), 78.4 (d,
J = 5.4 Hz, O-CH), 58.0 (d, J = 5.5 Hz, CH), 52.7 (OCH3), 28.4
Phosphates 15a,aЈ: Phosphates 15 have been prepared from rac-
VANOL and diethyl (S)-malate N,N,NЈ,NЈ-tetraisopropylphos-
phorodiamidite (S)-9 as described for 14a,aЈ. The corresponding
phosphites were obtained after 16 h heating at 40 °C [31P NMR
(202.5 MHz, CDCl3): δ = 148.4 and 144.3 ppm]. After oxidation,
the crude mixture was purified by chromatography on silica gel
(heptane/EtOAc = 6:4 to 4:6, 72% yield). Phosphates 15a and 15aЈ
were separated by semi-preparative HPLC on a Sunfire C18 re-
versed phase column, H2O/MeCN/Formic Acid (23:77:0.1). 15a:
retention time 16.6 min; 15aЈ: retention time 17.8 min.
15a: 31P NMR (202.5 Hz, CDCl3): δ = 2.0 ppm. 1H NMR
(500.1 MHz, CDCl3): δ = 8.65 (d, J = 8.4 Hz, 1 H), 8.51 (d, J =
8.4 Hz, 1 H), 7.83 (d, J = 8.1 Hz, 2 H), 7.71–7.65 (m, 2 H), 7.62–
7.59 (m, 2 H), 7.51 (s, 1 H), 7.50 (s, 1 H), 7.12–7.08 (m, 2 H), 6.95–
6.91 (m, 4 H), 6.48–6.46 (m, 4 H), 5.71–5.67 (m, 1 H, OCH), 4.37
(q, J = 7.2 Hz, 2 H, OCH2), 4.11 (q, J = 7.2 Hz, 2 H, OCH2), 3.05–
3.00 (m, 1 H), 2.95–2.90 (m, 1 H), 1.38 (t, J = 7.2 Hz, 3 H, Me),
(CMe ), 19.1 (CH ) ppm. IR: νmax = 3426, 3057, 3009, 2980, 1749,
˜
3
3
1718, 1490, 1364, 1301, 1290, 1165, 1017, 968, 761, 700 cm–1.
HRMS (ESI): m/z calcd. for C42H39NO8P [M + H]+ 716.2413;
found 716.2431. [α]2D0 = –77 (c = 1, CHCl3).
16aЈ: 31P NMR (202.5 Hz, CDCl3): δ = 2.1 ppm. 1H NMR
1.15 (t, J = 7.2 Hz, 3 H, Me) ppm. 13C NMR (125.8 MHz, CDCl3): (500.1 MHz, CDCl3): δ = 8.47 (d, J = 8.4 Hz, 1 H), 8.36 (d, J =
δ = 168.8 (CO), 168.4 (d, J = 3.6 Hz, CO), 146.3 (d, J = 11.8 Hz, 8.4 Hz, 1 H), 7.87 (d, J = 8.0 Hz, 1 H), 7.84 (d, J = 8.5 Hz, 1 H),
O-C), 144.9 (d, J = 9.2 Hz, O-C), 140.2 (C), 140.1 (C), 140.0 (C), 7.79 (t, J = 7.5 Hz, 1 H), 7.69–7.59 (m, 3 H), 7.53 (s, 1 H), 7.52 (s,
139.9 (C), 134.5 (C), 134.3 (C), 129.2 (CH), 129.1 (CH), 127.9 1 H), 7.13–7.09 (m, 2 H), 6.95–6.92 (m, 4 H), 6.49–6.46 (m, 4 H),
(CH), 127.8 (CH), 127.7 (CH), 127.6 (CH), 127.5 (CH), 127.2
(CH), 126.9 (CH), 126.7 (CH), 126.0 (C), 125.6 (d, J = 2.8 Hz, C),
123.2 (CH), 122.8 (CH), 122.3 (C), 74.3 (d, J = 5.3 Hz, OCH), 62.6
(OCH2), 61.4 (OCH2), 37.9 (d, J = 5.4 Hz, CH2), 14.3 (CH3), 14.2
5.60–5.54 (m, 1 H, OCH), 5.06 (d, J = 9.6 Hz, 1 H), 4.49 (d, J =
9.6 Hz, 1 H), 3.91 (s, 3 H, OMe), 1.46 (d, J = 6.6 Hz, 3 H, Me),
1.42 (s, 9 H, CMe3) ppm. 13C NMR (125.8 MHz, CDCl3): δ =
170.5 (CO), 156.0 (CO), 146.1 (d, J = 12.0 Hz, O-C), 145.2 (d, J =
9.2 Hz, O-C), 140.3 (C), 140.1 (C), 139.9 (C), 139.8 (C), 134.5 (C),
134.3 (C), 129.1 (CH), 128.1 (CH), 128.0 (CH), 127.9 (CH), 127.6
(CH), 127.5 (CH), 127.3 (CH), 126.8 (CH), 126.7 (CH), 125.7 (C),
125.5 (C), 122.7 (C), 122.5 (CH), 122.4 (CH), 80.4 (CMe3), 78.6 (d,
J = 5.5 Hz, OCH), 58.1 (d, J = 5.5 Hz, CH), 53.1 (OCH3), 28.4
(CH ) ppm. IR: ν
= 3056, 2985, 2937, 1760, 1738, 1489, 1363,
˜
3
max
1305, 1291, 1181, 1110, 1048, 1029, 761, 700 cm–1. HRMS (ESI):
m/z calcd. for C40H34O8P [M + H]+ 673.1991; found 673.2017.
[α]2D0 = –43 (c = 1, CHCl3).
15aЈ: 31P NMR (202.5 Hz, CDCl3): δ = 2.3 ppm. 1H NMR
(500.1 MHz, CDCl3): δ = 8.51 (d, J = 8.2 Hz, 1 H), 8.32 (d, J =
8.2 Hz, 1 H), 7.84–7.82 (m, 2 H), 7.68 (t, J = 7.8 Hz, 1 H), 7.64–
7.57 (m, 3 H), 7.52 (s, 1 H), 7.49 (s, 1 H), 7.12–7.08 (m, 2 H), 6.95–
6.91 (m, 4 H), 6.49–6.46 (m, 4 H), 5.76–5.71 (m, 1 H, OCH), 4.41–
4.33 (m, 2 H, OCH2), 4.19–4.11 (m, 2 H, O CH2), 3.05 (dd, J =
(CMe ), 18.9 (CH ) ppm. IR: νmax = 3430, 3056, 2979, 1752, 1721,
˜
3
3
1490, 1363, 1302, 1291, 1165, 1017, 968, 761, 700 cm–1. HRMS
(ESI): m/z calcd. for C42H39NO8P [M + H]+ 716.2413; found
716.2441. [α]2D0 = +118.5 (c = 1, CHCl3).
Representative Procedure for the Removal of the Chiral Auxiliary:
16.5, 4.8 Hz, 1 H, CH2), 2.96 (dd, J = 16.5, 6.4 Hz, 1 H, CH2), Phosphate 16a (36 mg, 0.05 mmol) was dissolved in CH2Cl2 (1 mL)
1.36 (t, J = 7.1 Hz, 3 H, Me), 1.19 (t, J = 7.1 Hz, 3 H, Me) ppm. and DBU (15 μL, 0.10 mmol) was added at room temperature. Af-
13C NMR (125.8 MHz, CDCl3): δ = 168.7 (CO), 146.0 (d, J = ter 20 min, crude 7b·DBU salt was purified by column chromatog-
Eur. J. Org. Chem. 4099, 4099–4106
© 4099 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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4105